Leptospirosis is a worldwide zoonotic disease that is caused by spirochetes in the genus Leptospira. This[unreadable] disease is now regarded as one of the important emerging infectious diseases worldwide, with the latest[unreadable] outbreaks occurring in Nicaragua, Brazil, India, Malaysia, Thailand and the United States. The clinical[unreadable] manifestations of leptospirosis are varied, ranging from a relatively mild flu-like illness to a severe syndrome[unreadable] of multi-organ infection that is associated with a high mortality. The ultimate goal of the proposed research is[unreadable] to increase our understanding of the basic biology and genetic differences between pathogenic and nonpathogenic[unreadable] strains of Leptospira, employing a range of genome based technologies. The specific hypothesis[unreadable] behind this proposal is that strains of Leptospira have major genetic differences that may be associated with[unreadable] their ability to cause disease, and that the pathogenic species alter the expression of appropriate genes in[unreadable] order to cope with the changes encountered in the environment. As such, we aim to increase our[unreadable] understaning of species diversity of different strains of Leptospira employing comparative genome[unreadable] hybridization techniques, and to understand the regulatory network(s) controlling gene expression that allow[unreadable] Leptospira species to sense and adapt to growth as either a parasitic or free-living organism. The Specific[unreadable] Aims are also designed to study the interaction between Leptospira and its host by monitoring the genomewide[unreadable] changes in leptospiral gene expression upon contact with host cells and to identify and characterize[unreadable] genes that are differentially expressed during host-pathogen interaction.[unreadable] An increased understanding of Leptospira biology will present opportunities to develop methods to address[unreadable] this pathogen, and will also serve as a model to understand the basic biology and pathogenic potential of[unreadable] emerging pathogenic species.